ACS Synthetic Biology,
Год журнала:
2024,
Номер
13(11), С. 3487 - 3496
Опубликована: Окт. 22, 2024
Manipulating
RNA
species
in
mammalian
cells
has
emerged
as
an
important
strategy
for
precise
gene
expression
control.
Here
we
review
recent
advances
precision
transcriptome
editing
with
a
focus
on
tools
that
engineer
specific
transcripts
abundance,
translation,
base
editing,
alternative
isoforms,
and
chemical
modifications.
While
some
of
these
methods
have
demonstrated
efficiency
therapeutically
relevant
cellular
or
vivo
models,
most
require
further
study
their
clinical
safety
efficacy.
Precision
engineering
holds
great
potential
both
mechanistic
biology
future
cell-based
therapeutic
applications.
Signal Transduction and Targeted Therapy,
Год журнала:
2023,
Номер
8(1)
Опубликована: Авг. 24, 2023
The
proper
transfer
of
genetic
information
from
DNA
to
RNA
protein
is
essential
for
cell-fate
control,
development,
and
health.
Methylation
DNA,
RNAs,
histones,
non-histone
proteins
a
reversible
post-synthesis
modification
that
finetunes
gene
expression
function
in
diverse
physiological
processes.
Aberrant
methylation
caused
by
mutations
or
environmental
stimuli
promotes
various
diseases
accelerates
aging,
necessitating
the
development
therapies
correct
disease-driver
imbalance.
In
this
Review,
we
summarize
operating
system
across
central
dogma,
which
includes
writers,
erasers,
readers,
reader-independent
outputs.
We
then
discuss
how
dysregulation
contributes
neurological
disorders,
cancer,
aging.
Current
small-molecule
compounds
target
modifiers
show
modest
success
certain
cancers.
methylome-wide
action
lack
specificity
lead
undesirable
biological
effects
cytotoxicity,
limiting
their
therapeutic
application,
especially
with
monogenic
cause
different
directions
changes.
Emerging
tools
capable
site-specific
manipulation
hold
great
promise
solve
dilemma.
With
refinement
delivery
vehicles,
these
new
are
well
positioned
advance
basic
research
clinical
translation
field.
Viruses,
Год журнала:
2024,
Номер
16(1), С. 127 - 127
Опубликована: Янв. 16, 2024
Epitranscriptomic
RNA
modifications
play
a
crucial
role
in
the
posttranscriptional
regulation
of
gene
expression.
N6-methyladenosine
(m6A)
is
most
prevalent
internal
modification
eukaryotic
and
plays
pivotal
fate.
m6A
regulated
by
group
cellular
proteins,
methyltransferases
(writers)
demethylases
(erasers),
which
add
remove
methyl
from
adenosine,
respectively.
recognized
RNA-binding
proteins
(readers)
that
specifically
bind
to
m6A-modified
RNA,
mediating
effects
on
stability,
splicing,
transport,
translation.
The
functional
significance
viral
an
active
area
virology
research.
In
this
review,
we
summarize
analyze
current
literature
HIV-1
multifaceted
functions
regulating
replication,
evading
innate
immune
responses
infection.
Furthermore,
briefly
discuss
future
directions
therapeutic
implications
mechanistic
studies
epitranscriptomic
modifications.
Wiley Interdisciplinary Reviews - RNA,
Год журнала:
2023,
Номер
15(1)
Опубликована: Сен. 6, 2023
Abstract
Despite
the
discovery
of
modified
nucleic
acids
nearly
75
years
ago,
their
biological
functions
are
still
being
elucidated.
N
6
‐methyladenosine
(m
A)
is
most
abundant
modification
in
eukaryotic
messenger
RNA
(mRNA)
and
has
also
been
detected
non‐coding
RNAs,
including
long
RNA,
ribosomal
small
nuclear
RNA.
In
general,
m
A
marks
can
alter
secondary
structure
initiate
unique
RNA–protein
interactions
that
splicing,
mRNA
turnover,
translation,
just
to
name
a
few.
Although
human
RNAs
have
known
exist
since
1974,
structures
methyltransferases
responsible
for
writing
established
only
recently.
Thus
far,
there
four
confirmed
catalyze
transfer
methyl
group
from
S
‐adenosylmethionine
(SAM)
position
adenosine,
producing
A:
methyltransferase‐like
protein
(METTL)
3/METTL14
complex,
METTL16,
METTL5,
zinc‐finger
CCHC‐domain‐containing
4.
Though
targets,
all
contain
Rossmann
fold
with
conserved
SAM‐binding
pocket,
suggesting
they
utilize
similar
catalytic
mechanism
transfer.
For
each
methyltransferases,
we
present
links
disease,
kinetic
mechanisms,
macromolecular
structures.
We
discuss
viruses
parasites,
assigning
transcriptome
specific
molecules
targeting
enzymes
hypermodified
humans.
Understanding
critical
steppingstone
toward
establishing
epitranscriptome
more
broadly
RNome.
This
article
categorized
under:
Interactions
Proteins
Other
Molecules
>
Protein‐RNA
Recognition
RNA‐Protein
Complexes
Interactions:
Functional
Implications
Cancers,
Год журнала:
2023,
Номер
15(13), С. 3307 - 3307
Опубликована: Июнь 23, 2023
Glioblastoma
is
the
most
prevalent
primary
brain
tumour
and
invariably
confers
a
poor
prognosis.
The
immense
intra-tumoral
heterogeneity
of
glioblastoma
its
ability
to
rapidly
develop
treatment
resistance
are
key
barriers
successful
therapy.
As
such,
there
an
urgent
need
for
greater
understanding
biology
in
order
guide
development
novel
therapeutics
this
field.
N6-methyladenosine
(m6A)
abundant
RNA
modifications
eukaryotes.
Studies
have
demonstrated
that
regulation
modification
altered
may
serve
regulate
diverse
mechanisms
including
glioma
stem-cell
self-renewal,
tumorigenesis,
invasion
evasion.
However,
precise
by
which
m6A
exert
their
functional
effects
poorly
understood.
This
review
summarises
evidence
disordered
discusses
downstream
on
fate.
wide-ranging
biological
consequences
raises
hope
cancer
therapies
can
be
targeted
against
mechanism.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Апрель 22, 2024
Abstract
In
therian
mammals,
inactivation
of
one
the
X-chromosomes
in
female
cells
(XX)
balances
dosage
X-linked
gene
expression
between
sexes,
resulting
monoallelic
genes
females
similar
to
males
(XY).
Therefore,
it
creates
a
imbalance
for
with
respect
biallelically
expressing
autosomal
(AA).
X-to-autosome
compensation
is
thought
be
achieved
by
transcriptional
upregulation
many
from
active
X-chromosome
both
sexes.
Here,
we
have
delineated
role
m6A
RNA
methylation
maintenance
variety
cell
types,
including
embryonic,
extra-embryonic
and
somatic
cells.
We
show
that
marks
tend
less
enriched
on
transcripts
compared
most
studied
types.
However,
our
analysis
demonstrates
plays
minor
compensation.
loss
does
not
affect
silencing
inactive-X
early
embryonic
lineages,
suggesting
dispensable
inactivation.
On
contrary,
depletion
affects
compensation,
however,
effect
occurs
lineage-specific
manner.
Taken
together,
study
that,
although
are
lowly
ones,
X-inactivation
has
contribution
